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| | <StructureSection load='3f2o' size='340' side='right'caption='[[3f2o]], [[Resolution|resolution]] 2.05Å' scene=''> | | <StructureSection load='3f2o' size='340' side='right'caption='[[3f2o]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3f2o]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F2O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F2O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3f2o]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F2O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F2O FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SPSB1, SSB1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3f2o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f2o OCA], [https://pdbe.org/3f2o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f2o RCSB], [https://www.ebi.ac.uk/pdbsum/3f2o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f2o ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3f2o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f2o OCA], [https://pdbe.org/3f2o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f2o RCSB], [https://www.ebi.ac.uk/pdbsum/3f2o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f2o ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SPSB1_HUMAN SPSB1_HUMAN]] Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.<ref>PMID:15601820</ref> [[https://www.uniprot.org/uniprot/VASA1_DROME VASA1_DROME]] Involved in translational control mechanisms operating in early stages of oogenesis. Required maternally in many stages of oogenesis, including cystocyte differentiation, oocyte differentiation, and specification of anterior-posterior polarity in the developing cysts. Essential for the formation and/or structural integrity of perinuclear nuage particles during germ cell formation. Required for gus, Fsn and aub accumulation at the posterior pole of the embryo. Required for the localization of vas to the perinuclear region of nurse cells.<ref>PMID:10678180</ref> <ref>PMID:11526087</ref> <ref>PMID:12479811</ref> <ref>PMID:14588248</ref> <ref>PMID:16630817</ref> <ref>PMID:18590813</ref> <ref>PMID:20123973</ref> <ref>PMID:3052853</ref> <ref>PMID:3140040</ref> <ref>PMID:8026330</ref> <ref>PMID:9521895</ref>
| + | [https://www.uniprot.org/uniprot/SPSB1_HUMAN SPSB1_HUMAN] Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.<ref>PMID:15601820</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Drosophila melanogaster]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Bountra, C]] | + | [[Category: Bountra C]] |
| - | [[Category: Bullock, A]] | + | [[Category: Bullock A]] |
| - | [[Category: Delft, F Von]]
| + | [[Category: Edwards AM]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Filippakopoulos P]] |
| - | [[Category: Filippakopoulos, P]] | + | [[Category: Keates T]] |
| - | [[Category: Keates, T]] | + | [[Category: Knapp S]] |
| - | [[Category: Knapp, S]] | + | [[Category: Murray JW]] |
| - | [[Category: Murray, J W]] | + | [[Category: Pike ACW]] |
| - | [[Category: Pike, A C.W]] | + | [[Category: Roos A]] |
| - | [[Category: Roos, A]] | + | [[Category: Savitsky P]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Sharpe T]] |
| - | [[Category: Savitsky, P]] | + | [[Category: Von Delft F]] |
| - | [[Category: Sharpe, T]] | + | [[Category: Weigelt J]] |
| - | [[Category: Weigelt, J]] | + | |
| - | [[Category: Apoptosis]] | + | |
| - | [[Category: Apoptosis-hydrolase complex]]
| + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Developmental protein]]
| + | |
| - | [[Category: Differentiation]]
| + | |
| - | [[Category: Helicase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Oogenesis]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| - | [[Category: Ubl conjugation pathway]]
| + | |
| Structural highlights
Function
SPSB1_HUMAN Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The mammalian SPRY domain- and SOCS box-containing proteins, SPSB1 to SPSB4, belong to the SOCS box family of E3 ubiquitin ligases. Substrate recognition sites for the SPRY domain are identified only for human Par-4 (ELNNNL) and for the Drosophila orthologue GUSTAVUS binding to the DEAD-box RNA helicase VASA (DINNNN). To further investigate this consensus motif, we determined the crystal structures of SPSB1, SPSB2, and SPSB4, as well as their binding modes and affinities for both Par-4 and VASA. Mutation of each of the three Asn residues in Par-4 abrogated binding to all three SPSB proteins, while changing EL to DI enhanced binding. By comparison to SPSB1 and SPSB4, the more divergent protein SPSB2 showed only weak binding to Par-4 and was hypersensitive to DI substitution. Par-4((59-77)) binding perturbed NMR resonances from a number of SPSB2 residues flanking the ELNNN binding site, including loop D, which binds the EL/DI sequence. Although interactions with the consensus peptide motif were conserved in all structures, flanking sites in SPSB2 were identified as sites of structural change. These structural changes limit high-affinity interactions for SPSB2 to aspartate-containing sequences, whereas SPSB1 and SPSB4 bind strongly to both Par-4 and VASA peptides.
Structural basis for Par-4 recognition by the SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4.,Filippakopoulos P, Low A, Sharpe TD, Uppenberg J, Yao S, Kuang Z, Savitsky P, Lewis RS, Nicholson SE, Norton RS, Bullock AN J Mol Biol. 2010 Aug 20;401(3):389-402. Epub 2010 Jun 16. PMID:20561531[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kamura T, Maenaka K, Kotoshiba S, Matsumoto M, Kohda D, Conaway RC, Conaway JW, Nakayama KI. VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases. Genes Dev. 2004 Dec 15;18(24):3055-65. PMID:15601820 doi:http://dx.doi.org/10.1101/gad.1252404
- ↑ Filippakopoulos P, Low A, Sharpe TD, Uppenberg J, Yao S, Kuang Z, Savitsky P, Lewis RS, Nicholson SE, Norton RS, Bullock AN. Structural basis for Par-4 recognition by the SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4. J Mol Biol. 2010 Aug 20;401(3):389-402. Epub 2010 Jun 16. PMID:20561531 doi:10.1016/j.jmb.2010.06.017
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